Mammals and insects share controlgenes for eye morphogenesis such as eyeless/Pax6 and sine oculis and possibly other members of the regulatory cascade required for eyemorphogenesis. Eyeless is a paired box (Pax) containing homedomain protein that is required for eye formation. When eyeless is ectopically expressed in imaginal discs other than the eye disc, ectopic eyes are formed, suggesting that eyeless expression is sufficient to direct differentiation of eyes in discs fated to become other organs. Because homologous genes are present in vertebrates, ascidians (sea squirts), insects, cephalopods (squids and octopus), and nemerteans (worms), eyeless may function as a master control gene for eye formation throughout the metazoa.

Another evolutionarily conserved gene expressed early in eye determination in Drosophila is sine oculis. Sine oculis is present at the birth of the eye optic primordium, and has a direct role in this process. The eye optic primordium is the site, in embryos, of formation of the eye-antennal optic disc. In mutants there is an increase in cell death in the region of the primordium. Movement of the primordium into the head is arrested at an early stage. A vertebrate homolog, Six3 from mice, is included in the Six/sine oculis subclass of homeobox genes. Early in development Six3 expression is restricted to the anterior neural plate. Later, once the longitudinal axis of the brain bends, Six3 mRNAis also found in structures derived from the anterior neural plate: the ectoderm of the nasal cavity, the olfactoryplacode, Rathke's pouch, and also the ventral forebrain, including the region of the optic recess,hypothalamus and optic vesicles.

The Drosophila retina is patterned by a morphogenetic wave driven by the Hedgehog signaling protein. In Drosophila, Hedgehog, secreted by the first neurons, induces neuronal differentiation and also induces hedgehog expression in nearby uncommitted cells, thereby propagating the wave. The zebrafish Hedgehog homolog, Sonic Hedgehog, is also expressed in the first retinal neurons, and Sonic Hedgehog drives a wave of neurogenesis across the retina, strikingly similar to the wave in Drosophila (Neumann, 2000).

Math5, a homolog of atonal acts during retinal histogenesis, after primary pattern formation in the anterior neural tube, specification of the optic primordia, and the major period of the optic cup growth has occurred. Like R8 cells in the fly eye, retinal ganglion cells are the first neurons in the vertebrate eye. Math5 mutant mice are fully viable, yet lack RGCs and optic nerves. Thus, two evolutionarily diverse eye types, Drosophila eyes and mammalian eyes, require atonal gene familyfunction for the earliest stages of retinal neuron formation. Math5 expression is dependent upon Pax6, which has been positioned near the top of a hierarchy for metazoan eye development. These results, like those for thehedgehog genes, show that functional homology in visual system development extends more deeply than Pax6. Finally, these results further establish an evolutionary parallel between vertebrate RGCs and fly R8 photoreceptors, the earliest-born neurons of bilaterian visual systems (Brown, 2001).